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Variation in the propensity to release endotoxin after cefuroxime exposure in different gram-negative bacteria: uniform and dose-dependent reduction by the addition of tobramycin

Goscinski, Gunilla ; Lundholm, Monica ; Odenholt, Inga LU and Sjolin, Jan (2003) In Scandinavian Journal of Infectious Diseases 35(1). p.40-46
Abstract
An aminoglycoside in combination with a beta-lactam antibiotic is often recommended for the treatment of severe infections. The aim of the present study was to study whether cefuroxime-induced endotoxin release could be reduced by addition of tobramycin in different Gram-negative bacteria and how endotoxin release was affected by bacterial killing rate and number of killed bacteria. Three Escherichia coli strains, 1 Klebsiella, 1 Salmonella and 1 Neisseria strain were exposed in vitro to 2, 10 and 50 x minimum inhibitory concentration of cefuroxime, tobramycin or a combination of both. The cefuroxime-induced endotoxin release in the 6 strains varied from 0.1 to 9.9 x 10(-3) EU/killed bacterium. By adding tobramycin, highly significant... (More)
An aminoglycoside in combination with a beta-lactam antibiotic is often recommended for the treatment of severe infections. The aim of the present study was to study whether cefuroxime-induced endotoxin release could be reduced by addition of tobramycin in different Gram-negative bacteria and how endotoxin release was affected by bacterial killing rate and number of killed bacteria. Three Escherichia coli strains, 1 Klebsiella, 1 Salmonella and 1 Neisseria strain were exposed in vitro to 2, 10 and 50 x minimum inhibitory concentration of cefuroxime, tobramycin or a combination of both. The cefuroxime-induced endotoxin release in the 6 strains varied from 0.1 to 9.9 x 10(-3) EU/killed bacterium. By adding tobramycin, highly significant reductions of 96%, 93%, 97%, 86% and 85% were seen in the 3 E. coli strains and in the Klebsiella and the Salmonella strain, respectively. In the Neisseria strain, the reduction was less. Increasing doses of tobramycin or the combination led to significant endotoxin release reduction in 4/6 strains. In conclusion, addition of tobramycin reduced penicillin-binding protein-3-beta-lactam binding-induced endotoxin release in all tested Gram-negative strains, despite a large interspecies variation in the propensity to release endotoxin. Besides broadening the spectrum and increasing the killing rate, this might be of benefit in the most severe forms of sepsis. (Less)
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author
; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Infectious Diseases
volume
35
issue
1
pages
40 - 46
publisher
Informa Healthcare
external identifiers
  • pmid:12685883
  • scopus:0037229909
ISSN
1651-1980
DOI
10.1080/0036554021000026983
language
English
LU publication?
no
id
d6124206-7361-4252-9fef-d05e0e9fc318 (old id 1127533)
date added to LUP
2016-04-01 16:08:05
date last changed
2022-01-28 17:33:36
@article{d6124206-7361-4252-9fef-d05e0e9fc318,
  abstract     = {{An aminoglycoside in combination with a beta-lactam antibiotic is often recommended for the treatment of severe infections. The aim of the present study was to study whether cefuroxime-induced endotoxin release could be reduced by addition of tobramycin in different Gram-negative bacteria and how endotoxin release was affected by bacterial killing rate and number of killed bacteria. Three Escherichia coli strains, 1 Klebsiella, 1 Salmonella and 1 Neisseria strain were exposed in vitro to 2, 10 and 50 x minimum inhibitory concentration of cefuroxime, tobramycin or a combination of both. The cefuroxime-induced endotoxin release in the 6 strains varied from 0.1 to 9.9 x 10(-3) EU/killed bacterium. By adding tobramycin, highly significant reductions of 96%, 93%, 97%, 86% and 85% were seen in the 3 E. coli strains and in the Klebsiella and the Salmonella strain, respectively. In the Neisseria strain, the reduction was less. Increasing doses of tobramycin or the combination led to significant endotoxin release reduction in 4/6 strains. In conclusion, addition of tobramycin reduced penicillin-binding protein-3-beta-lactam binding-induced endotoxin release in all tested Gram-negative strains, despite a large interspecies variation in the propensity to release endotoxin. Besides broadening the spectrum and increasing the killing rate, this might be of benefit in the most severe forms of sepsis.}},
  author       = {{Goscinski, Gunilla and Lundholm, Monica and Odenholt, Inga and Sjolin, Jan}},
  issn         = {{1651-1980}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{40--46}},
  publisher    = {{Informa Healthcare}},
  series       = {{Scandinavian Journal of Infectious Diseases}},
  title        = {{Variation in the propensity to release endotoxin after cefuroxime exposure in different gram-negative bacteria: uniform and dose-dependent reduction by the addition of tobramycin}},
  url          = {{http://dx.doi.org/10.1080/0036554021000026983}},
  doi          = {{10.1080/0036554021000026983}},
  volume       = {{35}},
  year         = {{2003}},
}